Molecular Biology - DNA Forms and Structures

Nucleic Acids

• Nucleic acids store and transmit genetic information.
• Two main types exist:
  • Deoxyribonucleic acid (DNA)
  • Ribonucleic acid (RNA)
• DNA holds the instructions for making proteins.
• RNA exists in various forms, aiding protein synthesis.

Central Dogma of Life

• Information flows from DNA to RNA to protein.
• This flow describes most organisms' molecular biology, except some viruses which use RNA as their genetic repository.

Brief History (of DNA research)

• 1859: Charles Darwin published On the Origin of Species.
• 1865: Gregor Mendel's research on heredity.
• 1869: Friedrich Miescher discovered DNA.
• 1902: Walter Sutton and Theodor Boveri proposed the chromosome theory.
• 1910: Thomas Hunt Morgan, Calvin Bridges demonstrated genes are on chromosomes.
• 1944: Oswald Avery, Colin McLeod, Maclyn McCarty identified DNA as the genetic material.
• 1953: James Watson, Francis Crick, Rosalind Franklin, and Maurice Wilkins determined DNA's structure.
• 1961: Sydney Brenner, Francois Jacob, Matthew Meselson discovered messenger RNA.
• 1966: Marshall Nirenberg, Gobind Khorana finished unraveling the genetic code.
• Subsequent events after 1966 include: the discovery of restriction enzymes, creation of first recombinant DNA in vitro, cloning of a sheep, determination of human genome sequence and others.

Component of Nucleic Acid

• Nucleic acids are polymers of nucleotides.
• Nucleotides consist of a phosphate group, a sugar, and a nitrogenous base.
• Nucleotides are held together by 3' and 5' phosphate bridges.

Nucleotide

• Nucleotides are the building blocks of nucleic acids.
• They're composed of a nitrogenous base, a pentose sugar, and a phosphate group.
• Nucleotides have various functions, including forming co-enzymes and participating in cellular energy reactions (e.g., ATP).
• Nucleosides are base + sugar. A nucleotide is a nucleoside + phosphate.

Nitrogenous Bases

• Nitrogenous bases in nucleotides are aromatic, heterocyclic compounds.
• Two types:
  • Purines (double ring)
  • Pyrimidines (single ring)
• Purines: Adenine (A), Guanine (G)
• Pyrimidines: Cytosine (C), Thymine (T), Uracil (U)

Major Nitrogenous Bases (in DNA & RNA)

• DNA and RNA share two purines (Adenine and Guanine).
• However, DNA contains thymine (T), and RNA contains uracil (U) as the pyrimidine counterpart.

Tautomeric Forms of Purines and Pyrimidines

• Tautomerism in nucleic acid bases involves proton shifts within the heterocyclic ring.
• Keto-enol and imino-amino tautomers are formed.
• These forms are important for base-pairing in DNA and RNA.

Other Biologically Important Bases

• These bases include variations of the major purines and pyrimidines (ex. 1-methyladenosine, inosine).

Sugars of Nucleic Acids

• Pentose sugars (ribose and deoxyribose) are central to nucleic acid structure.
• Ribose is in RNA, deoxyribose in DNA.
• The two sugars differ structurally only by one oxygen atom at the 2' carbon position.

Nomenclature of Nucleotides

• Add a pentose sugar to the base to form a nucleoside.
• Ribonucleosides form when the sugar is ribose.
• Deoxyribonucleosides form when the sugar is deoxyribose.
• Adding one or more phosphate groups to the nucleoside results in a nucleotide.
• Prime notation (' ) distinguishes sugar carbon positions from base nitrogen positions.

Nucleosides and Nucleotides

• A table summarizing the names of important nucleosides and nucleotides (RNA and DNA variants)

Nucleotide Analogs

• Synthetic compounds similar to nucleosides/nucleotides used in treating viral infections (such as HIV and Hepatitis C).

DNA - Polymer of deoxyribonucleotide

• Composed of monomeric units:
  • Deoxyadenylate (dAMP)
  • Deoxyguanylate (dGMP)
  • Deoxycytidylate (dCMP)
  • Deoxythymidylate (dTMP)
• Monomeric units joined by phosphodiester bridges.

DNA Double Helix

• Proposed by Watson and Crick in 1953.
• The double helix is a twisted ladder structure.
• Two strands are antiparallel.
• Strands held together by hydrogen bonds between complementary bases (A-T and G-C).
• The diameter of a DNA double helix is 20 Å.
• Each turn of the helix is 34 Å, containing 10 base pairs.
• A strand has hydrophobic bases inside, with hydrophilic phosphate backbone on the outside.
• Other forms of DNA include triple-strand, bent DNA (with different shapes and functions.)

Chargaff's Rule

• Equal amounts of purines and pyrimidines in a DNA molecule.
• The quantity of adenine equals the quantity of thymine, and the quantity of guanine equals the quantity of cytosine.

Conformation of DNA Double Helix

• DNA exists in many forms (e.g. B-form, A-form, Z-form).
• A and Z forms represent non standard forms, unlike the common B-form.
• These structural variations influence interaction and protein binding.

Properties of Major Forms of DNA

• Table summarizing the key properties of A-DNA, B-DNA, and Z-DNA forms.

Other Types of DNA

• Other conformations of DNA exist besides B-DNA, A-DNA, and Z-DNA
• These variations are the result of different base sequences and interactions.

Denaturation of DNA

• Hydrogen bonds holding the two strands of DNA together are broken, leading to the separation of strands (into single strands).
• Denaturation may result from pH change, temperature increase.
• The phosphate-sugar backbone is not broken during denaturation.
• The process can be quantifies by the increase in UV absorbance.